Caveolae are uniform vesicular invaginations of the cell membrane. Caveolin-1 is responsible for the formation of caveolae and plays a key role in membrane traffic and signal transduction. The contribution of caveolin-1 to carcinogenesis has been widely investigated; however, the expression pattern of caveolin-1 is controversial both in gastrointestinal and extraintestinal cancers. Most of the results based on cancer cell line experiments suggest that caveolin-1 might act as a tumor-suppressor gene. On the contrary, several studies on the expression of caveolin-1 in tumor tissues indicate a possible tumor-promoting effect of caveolin-1. In this article we summarize the divergent results of caveolin-1 expression in gastrointestinal and extraintestinal cancer regarding possible future therapeutic implications.